title: A T cell epitope-based vaccine protects against chlamydial infection in HLA-DR4 transgenic mice.
abstract: Vaccination with recombinant chlamydial protease-like activity factor (rCPAF) has been shown to provide robust protection against genital Chlamydia infection. Adoptive transfer of IFN-γ competent CPAF-specific CD4⁺ T cells was sufficient to induce early resolution of chlamydial infection and reduction of subsequent pathology in recipient IFN-γ-deficient mice indicating the importance of IFN-γ secreting CD4⁺ T cells in host defense against Chlamydia. In this study, we identify CD4⁺ T cell reactive CPAF epitopes and characterize the activation of epitope-specific CD4⁺ T cells following antigen immunization or Chlamydia challenge. Using the HLA-DR4 (HLA-DRB1*0401) transgenic mouse for screening overlapping peptides that induced T cell IFN-γ production, we identified at least 5 CPAF T cell epitopes presented by the HLA-DR4 complex. Immunization of HLA-DR4 transgenic mice with a rCPAFep fusion protein containing these 5 epitopes induced a robust cell-mediated immune response and significantly accelerated the resolution of genital and pulmonary Chlamydia infection. rCPAFep vaccination induced CPAF-specific CD4⁺ T cells in the spleen were detected using HLA-DR4/CPAF-epitope tetramers. Additionally, CPAF-specific CD4⁺ clones could be detected in the mouse spleen following Chlamydia muridarum and a human Chlamydia trachomatis strain challenge using these novel tetramers. These results provide the first direct evidence that a novel CPAF epitope vaccine can provide protection and that HLA-DR4/CPAF-epitope tetramers can detect CPAF epitope-specific CD4⁺ T cells in HLA-DR4 mice following C. muridarum or C. trachomatis infection. Such tetramers could be a useful tool for monitoring CD4⁺ T cells in immunity to Chlamydia infection and in developing epitope-based human vaccines using the murine model.
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center for Excellence in Infection Genomics, Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, United States; Department of Pathology and Department of Dental Medicine, Midwestern University, Downers Grove, IL 60515, United States.
authors.forename: Weidang
authors.initials: W
authors.lastname: Li
authors.forename: Ashlesh K
authors.initials: AK
authors.lastname: Murthy
authors.forename: Gopala Krishna
authors.initials: GK
authors.lastname: Lanka
authors.forename: Senthilnath L
authors.initials: SL
authors.lastname: Chetty
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.forename: James P
authors.initials: JP
authors.lastname: Chambers
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Forsthuber
authors.forename: M Neal
authors.initials: MN
authors.lastname: Guentzel
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology; D002692:Chlamydia trachomatis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000517:prevention & control; D060737:Reproductive Tract Infections / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D015804:HLA-DR4 Antigen; D007371:Interferon-gamma
keywords: CPAF; Chlamydia; Detection of antigen specific T cells; HLA-DR4 transgenic mice; HLA-DR4tg mice; IFU; T cell epitopes; Tetramer; chlamydial protease-like activity factor; inclusion-forming unit; rCPAF; rCPAFep; recombinant CPAF-epitope fusion protein